2kfx

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[[Image:2kfx.png|left|200px]]
 
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==Structure of the N-terminal domain of human cardiac troponin C bound to calcium ion and to the inhibitor W7==
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The line below this paragraph, containing "STRUCTURE_2kfx", creates the "Structure Box" on the page.
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<StructureSection load='2kfx' size='340' side='right'caption='[[2kfx]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2kfx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KFX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KFX FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=WW7:N-(6-AMINOHEXYL)-5-CHLORO-1-NAPHTHALENESULFONAMIDE'>WW7</scene></td></tr>
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{{STRUCTURE_2kfx| PDB=2kfx | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kfx OCA], [https://pdbe.org/2kfx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kfx RCSB], [https://www.ebi.ac.uk/pdbsum/2kfx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kfx ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[https://omim.org/entry/611879 611879]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:15542288</ref> Defects in TNNC1 are the cause of familial hypertrophic cardiomyopathy type 13 (CMH13) [MIM:[https://omim.org/entry/613243 613243]. A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:11385718</ref> <ref>PMID:16302972</ref> <ref>PMID:18572189</ref> <ref>PMID:19439414</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN] Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kf/2kfx_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kfx ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The calmodulin antagonist W7 binds to troponin C in the presence of Ca(2+) and inhibits striated muscle contraction. This study integrates multiple data into the structure of the regulatory domain of human cardiac troponin C (cNTnC) bound to Ca(2+) and W7. The protein-W7 interface is defined through a three-dimensional {(1)H,(13)C}-edited-{(1)H,(12)C}-detected NOESY NMR experiment, and other aspects of the structure are modeled as perturbations to previously known coordinates and restraints. The structure determination protocol optimizes the protein-W7 contacts prior to the introduction of protein-W7 steric interactions or conformational changes in the protein. The structure determination protocol gives families of conformers that all have an optimal docking as assessed by satisfaction of the target function. The structure supports the previously proposed troponin I blocking mechanism for the activity of W7 in striated muscle and suggests a role for the flexible tail of W7 in stabilization of the bound state. This clarifies the structure-activity relationships of W7 and implicates an electrostatically mediated component of activity in common analogues of W7, including the antipsychotic trifluoroperazine and the cardiotonic levosimendan.
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===Structure of the N-terminal domain of human cardiac troponin C bound to calcium ion and to the inhibitor W7===
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Structure of the Inhibitor W7 Bound to the Regulatory Domain of Cardiac Troponin C.,Hoffman RM, Sykes BD Biochemistry. 2009 May 21. PMID:19419198<ref>PMID:19419198</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_19419198}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2kfx" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 19419198 is the PubMed ID number.
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{{ABSTRACT_PUBMED_19419198}}
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==About this Structure==
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[[2kfx]] is a 1 chain structure of [[Troponin]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KFX OCA].
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==See Also==
==See Also==
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*[[Troponin]]
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*[[Troponin 3D structures|Troponin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:19419198</ref><ref group="xtra">PMID:10387074</ref><ref group="xtra">PMID:12060657</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hoffman, R M.B.]]
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[[Category: Large Structures]]
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[[Category: Sykes, B D.]]
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[[Category: Hoffman RMB]]
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[[Category: Acetylation]]
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[[Category: Sykes BD]]
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[[Category: Calcium]]
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[[Category: Calcium regulation]]
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[[Category: Cardiac]]
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[[Category: Cardiomyopathy]]
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[[Category: Cardiotonic drug]]
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[[Category: Disease mutation]]
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[[Category: Metal binding protein]]
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[[Category: Muscle protein]]
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[[Category: Polymorphism]]
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[[Category: Striated muscle]]
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[[Category: Troponin]]
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[[Category: W7]]
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Current revision

Structure of the N-terminal domain of human cardiac troponin C bound to calcium ion and to the inhibitor W7

PDB ID 2kfx

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